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In vivo CYP3A activ...
In vivo CYP3A activity and pharmacokinetics of imatinib in relation to therapeutic outcome in chronic myeloid leukemia patients
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Skoglund, Karin (author)
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- Richter, Johan (author)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine
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- Olsson-Strömberg, Ulla (author)
- Uppsala universitet,Hematologi
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- Bergquist, Jonas (author)
- Uppsala universitet,Analytisk kemi
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- Aluthgedara, Warunika (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi,Analytisk kemi
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- Ubhayasekera, S J Kumari A (author)
- Uppsala universitet,Analytisk kemi
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Vikingsson, Svante (author)
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Svedberg, Anna (author)
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- Söderlund, Stina (author)
- Uppsala universitet,Hematologi
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Sandstedt, Anna (author)
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Johnsson, Anders (author)
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Aagesen, Jesper (author)
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Alsenhed, Jonas (author)
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Hägg, Staffan (author)
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Peterson, Curt (author)
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Lotfi, Kourosh (author)
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Gréen, Henrik (author)
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(creator_code:org_t)
- 2016
- 2016
- English.
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In: Therapeutic Drug Monitoring. - 0163-4356 .- 1536-3694. ; 38:2, s. 230-238
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http://dx.doi.org/10...
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Abstract
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- BACKGROUND: CYP3A metabolic activity varies between individuals and is therefore a possible candidate of influence on the therapeutic outcome of the tyrosine kinase inhibitor imatinib in chronic myeloid leukemia (CML) patients. The aim of this study was to investigate the influence of CYP3A metabolic activity on the plasma concentration and outcome of imatinib in CML patients.METHODS: Forty-three CML patients were phenotyped for CYP3A activity using quinine as a probe drug and evaluated for clinical response parameters. Plasma concentrations of imatinib and its main metabolite, CGP74588, were determined using liquid chromatography-mass spectrometry.RESULTS: Patients with optimal response to imatinib after 12 months of therapy did not differ in CYP3A activity compared to non-optimal responders (quinine metabolic ratio of 14.69 and 14.70, respectively; P=0.966). Neither the imatinib plasma concentration nor the CGP74588/imatinib ratio was significantly associated with CYP3A activity.CONCLUSIONS: CYP3A activity does not influence imatinib plasma concentrations or the therapeutic outcome. These results indicate that even though imatinib is metabolized by CYP3A enzymes, this activity is not the rate-limiting step in imatinib metabolism and excretion. Future studies should focus on other pharmacokinetic processes so as to identify the major contributor to patient variability in imatinib plasma concentrations.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Keyword
- pharmacokinetics; chronic myeloid leukemia; imatinib; CGP74588; CYP3A
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Skoglund, Karin
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Richter, Johan
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Olsson-Strömberg ...
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Bergquist, Jonas
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Aluthgedara, War ...
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Ubhayasekera, S ...
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show more...
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Vikingsson, Svan ...
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Svedberg, Anna
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Söderlund, Stina
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Sandstedt, Anna
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Johnsson, Anders
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Aagesen, Jesper
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Alsenhed, Jonas
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Hägg, Staffan
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Peterson, Curt
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Lotfi, Kourosh
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Gréen, Henrik
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Pharmaceutical S ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
- Articles in the publication
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Therapeutic Drug ...
- By the university
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Uppsala University
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Lund University